thames valley chemotherapy regimens - tvscn

Thames Valley

Thames Valley Chemotherapy

Regimens

Lung Cancer

Thames Valley

Network Chemotherapy Protocols – Lung Cancer 2

Notes from the editor These regimens are available on the Network website www.tvcn.org.uk. Any correspondence about the regimens should be addressed to: Sally Coutts, Cancer Pharmacist, Thames Valley email: [email protected] Tel: 01865 857158 to leave a message Acknowledgements These regimens have been compiled by the Network Pharmacy Group in collaboration with the Lung TSSG with key contributions from Dr Nick Bates, Consultant Oncologist, ORH Dr Paul Rogers, Consultant Oncologist, RBFT Dr Joss Adams, Consultant Oncologist, RBFT Sally Punter, formerly Oncology Pharmacist, ORH Sandra Harding Brown, formerly Specialist Principal Pharmacist Oncology, ORH Alison Ashman, formerly Lead Pharmacist Thames Valley Cancer Network © Thames Valley Cancer Network. All rights reserved. Not to be reproduced in whole or in part without the permission of the copyright owner.

Thames Valley

Chemotherapy regimens – Lung Cancer 3

Thames Valley Chemotherapy Regimens Lung Cancer Network Chemotherapy regimens used in the management of Lung Cancer Date published: March 2015 Date of review: March 2017

Chemotherapy Regimens Name of protocol Indication Page List of amendments to this version 5

Notes 6

ACE Small Cell lung 7

CAV Small Cell lung 9

Carboplatin Etoposide Small cell lung 11

Cisplatin (75) Etoposide (100) Small cell lung 13

Cisplatin (60) Etoposide(120) Small cell lung 15

Topotecan oral Small cell lung 17

Afatnib Non small cell lung 19

Cisplatin (50) Etoposide (50) Non small cell lung 21

Cisplatin Vinorelbine with concurrent RT Non small cell lung 23

Gemcitabine Cisplatin i Non small cell lung 25

Cisplatin 40 RT Non small cell lung 27

Crizotinib Non small cell lung cancer 29

Docetaxel 75 Non small cell lung 31

Docetaxel (75) Cisplatin (75) Non small cell lung 33

Docetaxel (75) Carboplatin Non small cell lung 35

Erlotinib Non small cell lung 37

Gefitinib Non small cell lung 39

Gemcitabine (1200) Carboplatin Non small cell lung and small cell lung 41

Gemcitabine (1000) Non small cell lung 43

Paclitaxel weekly NSCLC 45

Vinorelbine (25) Carboplatin Non small cell lung 47

Vinorelbine (25) Cisplatin (80) Non small cell lung 49

Vinorelbine Non small cell lung 51

Vinorelbine (oral) Non small cell lung 52

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Name of protocol Page

Name of protocol Indication Name of protocol

Vinorelbine elderly (oral) Non small cell lung 54

Vinorelbine (oral) Cisplatin Non small cell lung 56

Vinorelbine (oral) Carboplatin Non small cell lung 57

Carboplatin Pemetrexed Non small cell lung, Mesothelioma 59

Cisplatin Pemetrexed Non small cell lung, Mesothelioma 61

Pemetrexed maintenance Non small cell lung 63

Pre and post hydration regimens 65

Common toxicity criteria 66

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List of amendments in this version Regimen type: Lung Tumours Date due for review: March 2017 Previous Version number: 3.3 This version number: 3.4 Table 1 Amendments

Page Amendment Made/ asked by

Table 2 New protocols to be approved and checked by TSSG included in this version Name of regimen Indication Reason / Proposer

Pemetrexed weekly NSCLC Dr Adams

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Notes 1. There is variation in practice in the administration of etoposide. In some hospitals this is only

given intravenously; in others it is given intravenously on day 1 and orally on days 2 and 3. The reason for using oral administration is lack of chemotherapy suite time. The absorption of oral etoposide is known to be erratic, with reduced efficacy in some patients, and severe toxicity in others and is not recommended. Chemotherapy resources should be reallocated to allow intravenous administration of etoposide in all appropriate patients.

2. Combinations of paclitaxel, docetaxel, gemcitabine or vinorelbine with a platinum have been recommended by NICE for first line chemotherapy in NSCLC. All four of the new drugs are in use across across the network.

3. NICE has recommended Pemetrexed for malignant mesothelioma for some groups of patients and first line treatment of NSCLC with adenocarcinoma and large cell undifferentiated carcinoma.

4. These protocols are likely to change as new evidence becomes available. Please ensure you are using the most up to date version of the protocols (as published on the TVCN website).

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ACE (SCLC) Indication: Has been used as first line treatment for SCLC but platinum/etoposide is preferred People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 DOXORUBICIN 40mg/2

IV bolus

CYCLOPHOSPHAMIDE 600mg/m2 IV bolus

ETOPOSIDE 100mg/m2 infusion in 1000ml sodium chloride 0.9% over 60 minutes

Day 2 ETOPOSIDE 100mg/m2 infusion in 1000ml sodium chloride 0.9% over 60 minutes

Day 3 ETOPOSIDE 100mg/m2 infusion in 1000ml sodium chloride 0.9% over 60 minutes NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 200mg/m2

PO but is not recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary.

Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If AST is 2-3 x ULN give 75% dose If AST is >3 x ULN give 50% dose Maximum cumulative dose = 450 mg/m2

(in normal cardiac function)

= 400 mg/m2 (in patients with cardiac dysfunction or exposed to mediastinal irradiation)

Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision

ACE Lung TSSG Chair Authorisation: Date:

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Cyclophosphamide: GFR >20ml/min give 100% dose GFR 10-20ml/min give 75% dose GFR <10ml/min give 50% dose INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Liver function tests (LFT) Serum Creatinine 2) Non urgent blood tests Tests relating to disease response/progression ECG (possibly ECHO) required if patient has preexisting cardiac disease (Doxorubicin) CONCURRENT MEDICATION ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cyclophosphamide may irritate bladder, drink copious volumes of water. Cardiotoxicity – Monitor cardiac function to minimise the risk of anthracycline induced cardiac failure. Doxorubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue.

REFERENCES 1. Aisner J et al. Cancer Treat Rep 1982; 66: 221 230 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic

impairment. 2009, The North London Cancer Network.

ACE Lung TSSG Chair Authorisation: Date:


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CAV (SCLC) Indication: First line treatment for SCLC in patients not able to tolerate platinum and etoposide (e.g. performance status of 3). Can also be used as second line treatment after relapse. People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 VINCRISTINE 1.3mg/m2

(max. 2 mg) in 50ml sodium chloride 0.9% IV over 10 mins

DOXORUBICIN 40mg/m2 IV bolus

CYCLOPHOSPHAMIDE 750 mg/m2

IV bolus Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Vincristine: If patient complains of tingling of fingers and/or toes, discuss. Bilirubin 25-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L and normal AST give 50% dose Bilirubin >51micromol/L and AST >180u/L omit Doxorubicin: Dose reduce in severe renal impairment. Bilirubin 20-50micromol/L give 50% dose Bilirubin 51-85micromol/L give 25% dose Bilirubin >85micromol/L omit If AST is 2-3 x ULN give 75% dose If AST is >3 x ULN give 50% dose Maximum cumulative dose = 450 mg/m2

(in normal cardiac function)

= 400 mg/m2(in patients with cardiac dysfunction or exposed to mediastinal irradiation)

Cyclophosphamide: GFR >20ml/min give 100% dose GFR 10-20ml/min give 75% dose GFR <10ml/min give 50% dose CAV Lung TSSG Chair Authorisation:

Date:


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INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Liver function tests (LFT) Serum Creatinine 2) Non urgent blood tests Tests relating to disease response/progression ECG (possibly ECHO) required if patients has pre-existing cardiac disease (Doxorubicin) CONCURRENT MEDICATION ANTIEMETIC POLICY High emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Cardiotoxicity – Monitor cardiac function to minimise the risk of anthracycline induced cardiac failure. Doxorubicin may be stopped in future cycles if signs of cardiotoxicity e.g. cardiac arrhythmias, pericardial effusion, tachycardia with fatigue. Cyclophosphamide may irritate bladder, drink copious volumes of water.

REFERENCES 1. Greco FA et al. Am J Med 1979; 66: 625 630. 2. Roth BJ et al. J Clin Oncol 1992; 10: 282291 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


CAV Lung TSSG Chair Authorisation: Date:


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Carboplatin Etoposide (SCLC) Indication: Standard first line treatment for SCLC People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 CARBOPLATIN AUC 5 infusion in 500ml glucose 5% infusion over 60 minutes

Dose (mg) = AUC x (GFR+25) ETOPOSIDE 100mg/m2

infusion in 1000ml sodium chloride 0.9% over 60 minutes



NB Day 2 and 3 can be given orally ETOPOSIDE 100mg/m2 bd

PO but is not recommended as

oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Etoposide doses <200mg may be administered in 500ml sodium chloride 0.9%

Ideally EDTA GFR should be used, Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If GFR / calculated CrCl = or < 20ml/min contraindicated. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Carboplatin/ etoposide

Lung TSSG Chair Authorisation: Date:


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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Ideally EDTA GFR should be used (Carboplatin) Creatinine clearance (GFR) calculated, at the Consultants discretion Liver function tests (LFT) 2) Non urgent blood tests. Tests relating to disease response/progression CONCURRENT MEDICATION FOR PREVENTION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours. ANTIEMETIC POLICY Moderate emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Ototoxicity - monitor Neurotoxicity – monitor. REFERENCES 1. Skarlos DV et al. Ann Oncol 1994; 5: 601 607 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic

impairment. 2009, The North London Cancer Network. 3. Study 12/14

Carboplatin/ etoposide



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Cisplatin (75) Etoposide (100) (SCLC) Indication: Standard first line treatment for SCLC at ORH with concurrent radiotherapy People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 Pre-hydration

ETOPOSIDE 100mg/m2 infusion in 1000ml sodium chloride 0.9% over 60 minutes

CISPLATIN 75mg/m2

infusion in 1000ml sodium chloride 0.9% over 2 hours Post hydration



NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 200mg/m2/day but is not

recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Etoposide doses <200mg may be administered in 500ml sodium chloride 0.9%

Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min omit dose If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cisplatin 75 / etoposide 100



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated, or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

REFERENCES 1. Evans WK et al. J Clin Oncol 1985; 3: 1471 1477. Roth BJ et al. J Clin Oncol 1992; 10: 282291 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Cisplatin 75 / etoposide 100



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Cisplatin (60) with Etoposide (120) (SCLC) Indication: Standard first line treatment for SCLC at RBH and HWP People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) DRUG REGIMEN Day 1 Pre-hydration ETOPOSIDE 120mg/m2

infusion in 1000ml sodium chloride 0.9% over 60 minutes CISPLATIN 60mg/m2

infusion in 1000ml sodium chloride 0.9% over 2 hours

Post-hydration Day 2 ETOPOSIDE 120mg/m2


Day 3 ETOPOSIDE 120mg/m2

infusion in 1000ml sodium chloride 0.9% over 60 minutes NB Day 2 and 3 etoposide can be given orally ETOPOSIDE 240mg/m2/day but is not

recommended as oral absorption is variable (it may cause reduced efficacy or severe toxicity in patients), the intravenous route is preferred, however for logistical reasons the oral route may be necessary. Etoposide doses <200mg may be administered in 500ml sodium chloride 0.9%

Cycle Frequency: Every 21 days Number of cycles: Usually 6 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision Cisplatin 60 /etoposide 120



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INVESTIGATIONS 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated, or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests: tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk days 2 and 3 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

REFERENCES 1. Evans WK et al. J Clin Oncol 1985; 3: 1471 1477. 2. Roth BJ et al. J Clin Oncol 1992; 10: 282291 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Cisplatin 60 /etoposide 120 in



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TOPOTECAN (oral) (SCLC) Indication: Relapsed small cell lung cancer (second line) People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) NICE: Oral topotecan is recommended as an option only for people with relapsed small-cell lung cancer for whom:re-treatment with the first-line regimen is not considered appropriate and the combination of cyclophosphamide, doxorubicin and vincristine (CAV) is contraindicated (for details of the contraindications to CAV see the summary of product characteristics for each of the component drugs). DRUG REGIMEN Days 1 to 5 Topotecan 2.3mg/m2 orally daily Cycle Frequency: Every 3 weeks until progression DOSE MODIFICATIONS Topotecan: Renal impairment CrCl >40ml/min give 100% dose CrCl 20-39ml/min give 50% dose CrCl <20ml/min contraindicated Hepatic impairment Bilirubin <170micromol/L give 100% dose Bilirubin >170micromol/L Clinical decision Neutropenia Standard oncology practice for the management of neutropenia is either to administer topotecan with other medications (e.g. G-CSF) or to dose reduce to maintain neutrophil counts. In this clinical situation, dose reduction is usually appropriate If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 109/l) for seven days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the dose should be reduced by 0.4 mg/m2/day to 1.9 mg/m2/day (or subsequently down to 1.5 mg/m2/day if necessary).

Topotecan oral



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INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration

Give Discuss Hb x g/dL 9 < 9 Plt x 109/L 100 < 100 Neutrophils x 109/L 1.5 < 1.5 1st treatment, <1.0 for subsequent treatment Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTIEMETIC POLICY Low emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Febrile neutropenia Interstitial lung disease Diarrhoea - may be severe and on occasion associated with neutropenic colitis. It should be managed aggressively with anti-diarrhoeals, antibiotics, maintenance of hydration and admission if required. REFERENCES 1. NICE TA 184 November 2009 2. SPC November 2010

Topotecan oral



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AFATINIB (NSCLC) Indication: Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-positive locally advanced or metastatic Non Small Cell Lung Cancer where the person has not previously had an EGFR-TK inhibitor NICE TA310 Afatinib is recommended as a possible treatment for adults with locally advanced or metastatic non-small-cell lung cancer if: their cancer tests positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and they have not had a type of drug called an EGFR-TK inhibitor before No National regimen name (April 2013) DRUG REGIMEN Day 1 Afatinib 40mg orally daily (may be escalated to 50mg/daily) Cycle Frequency: Until disease progression or unacceptable toxicity. Review every 2 months by CTscan DOSE MODIFICATIONS If dose reduction required reduce dose by 10mg increments to 20mg Afatinib: Renal impairment Severe renal impairment (CrCl <30ml/min) not recommended. Hepatic impairment Exposure to afatinib is not significantly changed in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Adjustments to the starting dose are not necessary in patients with mild or moderate hepatic impairment. This medicinal product has not been studied in patients with severe (Child Pugh C) hepatic impairment. Treatment in this population is not recommended

Afatinib Lung TSSG Chair Authorisation: Date:


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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Take one hour before or two hours after meals. Some of the following may be required for treatment of the skin rash: E45 / Diprobase, Hydrocortisone 1%/2.5%, Clindamycin gel 1%, Oxytetracycline 500mg po bd (for 2 weeks) Prednisolone 25mg po od for 7 days then reducing by 5mg per day to stop. ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin rash – initial rash may be severe. Diarrhoea –Proactive management of diarrhoea including adequate hydration combined with anti-diarrhoeal medicinal products especially within the first 6 weeks of the treatment is important and should start at first signs of diarrhoea. REFERENCES Afatinib Named Patient Use (1200.52) Information Pack Sept 2011 SPC January 2014

Afatinib Lung TSSG Chair Authorisation: Date:


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Cisplatin (50) Etoposide (50) (NSCLC) Indication: Superior sulcus non-small cell carcinoma DRUG REGIMEN Day 1, 8, 29 & 36 Pre-hydration

CISPLATIN 50mg/m2

infusion in 1000ml sodium chloride 0.9% over 2 hours Post hydration

Days 1 to 5 ETOPOSIDE 50mg/m2 infusion in 500ml sodium chloride 0.9% over 60 minutes

Days 29 to 33 ETOPOSIDE 50mg/m2 infusion in 500ml sodium chloride 0.9% over 60 minutes

This regimen is given concurrently with radiotherapy (45Gy in 25 fractions, given 5 days per week over 5 weeks. Radiation and chemotherapy to start within 24 hours of each other. Number of cycles: 1 cycle DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Etoposide: CrCl >50ml/min give 100% dose CrCl 15-50ml/min give 75% dose CrCl <15ml/min give 50% dose Bilirubin 26-51micromol/L or AST 60-180u/L give 50% dose Bilirubin >51micromol/L or AST >180u/L Clinical decision

Cisplatin / etoposide sulcus



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk days 1, 8, 29 and 36 Low emetic risk days 2 to 5 and days 30 to 33 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

REFERENCES 1. Rusch VW, Giroux KJ, Kraut JC et al. Induction Chemoradiation and Surgical Resection for

Superior Sulcus Non-Small Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 25: 313-318, 2007.

Cisplatin / etoposide sulcus



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Cisplatin Vinorelbine (NSCLC) Indication: Non-small cell lung cancer suitable for chemoradiotherapy DRUG REGIMEN Days 1 to 4 & 22 to 25 Pre-hydration

CISPLATIN 20mg/m2

infusion in 1000ml sodium chloride 0.9% over 2 hours (with fractions 1-4 and 16-19 of radiotherapy) Post hydration

Days 1, 8, 19 & 26 VINORELBINE 15mg/m2 infusion in 50ml sodium chloride 0.9% over 10 minutes

prior to radiotherapy on fractions 1, 6, 15, and 20 Radiotherapy should be given no more than 6 hours after starting the cisplatin Number of cycles: 1 cycle of 42 days DOSE MODIFICATIONS Haematological ANC X109/L PLATELETS X109/L VINORELBINE CISPLATIN >1.5 and >100 100% 100% 1.0-1.5 or 60-100 omit 100% <1.0 or <60 omit omit Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Vinorelbine: If bilirubin > 2 x ULN or AST/ALT > 5 x ULN reduce to 66.6%

Cisplatin / vinorelbine RT



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion (Cisplatin) Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. Ciprofloxacin 500mg po BD days 8 to 20 and 29 to 41 ANTIEMETIC POLICY Highly emetogenic day 1-4 and 22-25 Minimal emetogenic risk days 8, 19 and 26 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

REFERENCES SOCCAR trial Cisplatin / vinorelbine RT


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GEMCITABINE CISPLATIN (NSCLC) NICE guidance – www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: Standard combination for palliative treatment of NSCLC Unknown primary if appropriate DRUG REGIMEN Day 1 PRE-HYDRATION

GEMCITABINE 1250mg/m2 infusion in 250ml sodium chloride 0.9% over 30 minutes

CISPLATIN 80mg/m2 infusion in 1000ml sodium chloride 0.9% over 2 hours

POST-HYDRATION Day 8 GEMCITABINE 1250mg/m2


Cycle Frequency: Every 21 days Number of cycles: up to 4 (subject to tolerance and response) DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. Gemcitabine: CrCl <30ml/min consider dose reduction (Clinical decision) If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2 Neutrophils >1.5x10x9/L and platelets >100x10x9/L give 100% dose (Day 1 and 8) Neutrophils 0.5-1.5x10x9/L or platelets 50-100x10x9/L give 75% dose (Day 8 only) or delay based on clinical assessment (Day 1 and 8) Neutrophils <0.5x10x9/L or platelets <50x10x9/L delay treatment (Day 1) or omit treatment (Day 8). Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Omit if treatment is delayed for more than 4 weeks but continue with Cisplatin Cisplatin / Gemcitabine



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5

Liver function tests (LFT)

Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion (Cisplatin). 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk day 1 Low emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Diarrhoea – see dose modifications treat with loperamide or codeine. Mucositis – see dose modifications use routine mouth care. REFERENCES 1. Giaccone G et al. Seminars in Oncology 2002; 29 (3) Supp 9: 47 49 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Cisplatin / Gemcitabine



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CISPLATIN (40) concurrent radiotherapy (NSCLC) Indication: Unresectable stage IIIA/IIIB Non small cell lung cancer concurrently with radical radiotherapy after neoadjuvant chemotherapy with 2 cycles of cisplatin/vinorelbine. DRUG REGIMEN Day 1 Pre-hydration

CISPLATIN 40mg/m2 infusion in 1000ml sodium chloride 0.9% over 2 hours

Post-hydration Cycle Frequency: Every week for 4 weeks. Start early in Radiotherapy. DOSE MODIFICATIONS Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated, or EDTA at the Consultants discretion. (Cisplatin) Consider transfusions to keep Hb > 12 x g/dL 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. Cisplatin + radiotherapy



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ANTIEMETIC POLICY Moderately emetic risk. ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. SchaakeKoning C et al. N Eng J Med 1992; 326: 524 530 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Cisplatin + radiotherapy



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CRIZOTINIB (NSCLC) Indication: for the treatment of adults with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). Ensure individual funding has been obtained prior to prescribe. DRUG REGIMEN Day 1 Crizotinib 250mg orally twice daily Cycle Frequency: Continuously DOSE MODIFICATIONS Crizotinib: Renal impairment No starting dose adjustment is recommended for patients with mild (creatinine clearance [CLcr] 60 to 90 mL/min) and moderate renal impairment (CLcr 30 to 60 mL/min). No data are available in patients with severe and end-stage renal disease (see section 5.2) and therefore, no formal dosing recommendation could be made. Hepatic impairment Clinical studies that were conducted excluded patients with AST or ALT >2.5 x upper limit of normal (ULN), or if due to underlying malignancy, >5.0 x ULN or with total bilirubin >1.5 x ULN. Treatment with Crizotinib should be used with caution in patients with mild and moderate hepatic impairment and should not be used in patients with severe hepatic impairment, CTCAE grade Treament

Grade 3 or 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation with Grade ≤1 total bilirubin

Withhold until recovery to Grade ≤1 or baseline, then resume at 200 mg twice dailyb

Grade 2, 3 or 4 ALT or AST elevation with concurrent Grade 2, 3 or 4 total bilirubin elevation (in the absence of cholestasis or hemolysis)

Permanently discontinue

Any Grade pneumonitisc Permanently discontinue

Grade 3 QTc prolongation Withhold until recovery to Grade ≤1, then resume at 200 mg twice dailyb

Grade 4 QTc prolongation Permanently discontinue

Crizotinib Lung TSSG Chair Authorisation:

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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS REFERENCES

Crizotinib Lung TSSG Chair Authorisation: Date:


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DOCETAXEL (75) (NSCLC) NICE guidance www.nice.org.uk Docetaxel monotherapy should be considered where second line treatment is appropriate for patients with locally advanced or metastatic NSCLC when relapse has occurred after prior chemotherapy. Indication: Second line therapy for NSCLC after failure of platinum containing chemotherapy DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE 8 mg BD starting 24 hours before chemotherapy

(or 20mg IV on day of chemotherapy) and 8mg bd post-chemotherapy for 2 days (for patients who are unable to tolerate high doses of steroids 4mg doses may be considered) DOCETAXEL 75mg/m2


Cycle Frequency: Every 21 days Number of cycles: Individualised but not usually more than 6 (subject to tolerance and response) DOSE MODIFICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Patients who have both elevations of transaminase (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: the SPC recommended dose is 75mg/m2. Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests Tests relating to disease response/progression Docetaxel Lung TSSG Chair Authorisation:

Date:


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CONCURRENT MEDICATION Ensure pre-medication is given. This can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions ANTIEMETIC POLICY Low emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. REFERENCES 1. Shepherd F et al. J Clin Oncol 2000; 18: 2095 2103. Fossella F et al. J Clin Oncol 2000; 18:

2354 2362 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Docetaxel Lung TSSG Chair Authorisation: Date:


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DOCETAXEL (75) CISPLATIN (75) (NSCLC) NICE guidance www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: First line therapy for NSCLC DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE 8 mg BD starting 24 hours before chemotherapy

(or 20mg IV on day of chemotherapy) and 8mg bd post-chemotherapy for 2 days (for patients who are unable to tolerate high doses of steroids 4mg doses may be considered) Pre-hydration DOCETAXEL 75mg/m2 in 250ml sodium chloride 0.9% over 60 minutes CISPLATIN 75mg/m2 in 1000ml sodium chloride 0.9% infusion over 2 hours

Post-hydration Cycle Frequency: Every 21 days Number of cycles: 4 to 6 cycles DOSE MODIFICATIONS Docetaxel: Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Patients who have both elevations of transaminase (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: recommended SPC dose is 75mg/m2. Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated. Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration.

Docetaxel + cisplatin



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion. 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Docetaxel - Ensure pre-medication is given. This can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions Cisplatin - Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. ANTIEMETIC POLICY High emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Docetaxel - Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Shepherd F et al. J Clin Oncol 2000; 18: 2095 2103. 2. Fossella F et al. J Clin Oncol 2000; 18: 2354 2362 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Docetaxel + cisplatin



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DOCETAXEL (75) CARBOPLATIN (NSCLC) NICE guidance www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: First line therapy for NSCLC DRUG REGIMEN Day 1 PREMEDICATION: DEXAMETHASONE 8 mg BD starting 24 hours before chemotherapy

(or 20mg IV on day of chemotherapy) and 8mg bd post-chemotherapy for 2 days (for patients who are unable to tolerate high doses of steroids 4mg doses may be considered) DOCETAXEL 75mg/m2 in 250ml sodium chloride 0.9% over 60 minutes CARBOPLATIN AUC5 in 500ml glucose 5% infusion over 60 minutes

Cycle Frequency: Every 21 days Number of cycles: 4 to 6 cycles DOSE MODIFICATIONS Docetaxel: Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Patients who have both elevations of transaminase (ALT and/or AST) > 1.5 x ULN and ALP > 2.5 x ULN: recommended SPC dose is 75mg/m2. Patients with serum bilirubin > ULN and/or ALT and AST > 3.5 x ULN associated with ALP > 6 x ULN: docetaxel should not be used unless strictly indicated. Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If EDTA GFR = or < 20ml/min contraindicated

Docetaxel + carboplatin



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) EDTA at the Consultants discretion. 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Docetaxel - Ensure pre-medication is given. This can reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions Ototoxicity - monitor Neurotoxicity – monitor. ANTIEMETIC POLICY Moderate emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Docetaxel - Discuss if severe cutaneous reactions, peripheral neuropathy or fluid retention after previous course. Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Shepherd F et al. J Clin Oncol 2000; 18: 2095 2103. 2. Fossella F et al. J Clin Oncol 2000; 18: 2354 2362 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Docetaxel + carboplatin



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ERLOTINIB (NSCLC) Indication: Locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Factors associated with prolonged survival should be taken into account when prescribing erlotinib. NICE TA162 Erlotinib is recommended as an alternative to docetaxel for patients with non-small-cell lung cancer (NSCLC) who have already tried one chemotherapy regimen but it has not worked. Erlotinib should be used only when the manufacturer provides the drug at the same overall treatment cost as docetaxel. This cost includes the cost of giving the drug, treatments for any side effects and the cost of monitoring patients to check that treatment is working. NICE recommends erlotinib as a possible first-line treatment (that is, if you have not had drug treatment before) for some people with locally advanced or metastatic non-small-cell lung cancer. DRUG REGIMEN Day 1 Erlotinib 150mg orally daily Cycle Frequency: Initial review after 1 or 2 weeks of treatment then review every month until stable then review every 2 months DOSE MODIFICATIONS If dose reduction required reduce dose to 100mg daily Erlotinib: Renal impairment Severe renal impairment - erlotinib not recommended. Hepatic impairment Mild – moderate hepatic impairment – dose reduction or interruption of erlotinib should be considered if severe adverse reactions occur. Severe hepatic impairment – erlotinib not recommended

Erlotinib Lung TSSG Chair Authorisation: Date:


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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression

CONCURRENT MEDICATION Take one hour before or two hours after meals. Some of the following may be required for treatment of the skin rash: E45 / Diprobase, Hydrocortisone 1%/2.5%, Clindamycin gel 1%, Oxytetracycline 500mg po bd (for 2 weeks) Prednisolone 25mg po od for 7 days then reducing by 5mg per day to stop. ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin rash – initial rash may be severe. Diarrhoea – dose reduction may be required. Moderate or severe diarrhoea may require loperamide REFERENCES 1. Erlotinib in previously treated non-small cell lung cancer. Shepherd FA, Pereira JR, Ciuleanu, T

et al. N Engl J Med 2005;353; 123-132

Erlotinib Lung TSSG Chair Authorisation: Date:


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GEFITINIB (NSCLC) Indication: Locally advanced or metastatic non small cell lung cancer, first line NICE: Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if: they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation. DRUG REGIMEN Day 1 Gefitinib 250mg orally daily Cycle Frequency: Continuous treatment DOSE MODIFICATIONS Gefitinib: Renal imparment CrCl ≤20ml/min caution is advised Hepatic impairment Patients with moderate to severe hepatic impairment due to cirrhosis have increased plasma concentrations of gefitinib. These patients should be closely monitored for adverse events. Plasma concentrations were not increased in patients with elevated aspartate transaminase (AST), alkaline phosphatase or bilirubin due to liver metastases. INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration

Give Discuss Hb x g/dL 10 < 10 Plt x 109/L 100 < 100 Neutrophils x 109/L 1.5 < 1.5 Blood tests should initially be performed 4 weekly, but later in the treatment course can be done less often in stable patients. Creatinine Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression

Gefitinib Lung TSSG Chair Authorisation: Date:


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CONCURRENT MEDICATION Take at the same time each day. Swallow whole or disperse tablets in half a glass of water (noncarbonated) without crushing it. The glass should be swirled occasionally, until the tablet is dispersed (this may take up to 20 minutes). The dispersion should be drunk immediately after dispersion is complete (i.e. within 60 minutes). The glass should be rinsed with half a glass of water, which should also be drunk. ANTIEMETIC POLICY Minimal emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Skin rash Diarrhoea Elevation in ALT REFERENCES 1. Gefitinib SPC July 2009 2. NICE TA 192 July 2010

Gefitinib Lung TSSG Chair Authorisation: Date:


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GEMCITABINE (1200) CARBOPLATIN (NSCLC and SCLC) NICE guidance www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine should each be considered, with a platinum drug, as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. People with small-cell lung cancer should have treatment initiated within 2 weeks of the pathological diagnosis. (NICE) Indication: Standard combination for palliative treatment of NSCLC / SCLC Unknown primary if appropriate DRUG REGIMEN Day 1 GEMCITABINE 1200mg/m2

infusion in 250-500ml sodium chloride 0.9% over 30 minutes

CARBOPLATIN (AUC 5*) infusion in 500ml glucose 5% over 30-60 minutes Dose = (25 + GFR) x AUC

Day 8 GEMCITABINE 1200mg/m2 infusion in 250ml sodium chloride 0.9% over 30 minutes

Cycle Frequency: Every 21 days Number of cycles: Up to 4 for NSCLC and up to 6 for SCLC (subject to tolerance and response) NB * EDTA GFR should be used, If GFR is measured or EDTA then: AUC = 5 If calculated from serum creatinine the result is less accurate DOSE MODIFICATIONS Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If GFR/ calculated CrCl = or < 20ml/min contraindicated

Gemcitabine: CrCl <30ml/min consider dose reduction (Clinical decision) If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2 Neutrophils >1.5x10x9/L and platelets >100x10x9/L give 100% dose (Day 1 and 8) Neutrophils 0.5-1.5x10x9/L or platelets 50-100x10x9/L give 75% dose (Day 8 only) or delay based on clinical assessment (Day 1 and 8) Neutrophils <0.5x10x9/L or platelets <50x10x9/L delay treatment (Day 1) or omit treatment (Day 8). Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose Omit if treatment is delayed for more than 4 weeks but continue with Carboplatin Gemcitabine /carboplatin



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Liver function tests (LFTs)

GFR should be measured using EDTA clearance. Estimating creatinine clearance from the serum creatinine, weight and age is less accurate. 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours. ANTIEMETIC POLICY Moderate emetic risk day 1 Low emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications treat with loperamide or codeine. Mucositis – see dose modifications use routine mouth care. Ototoxicity - monitor Neurotoxicity – monitor REFERENCES 1. Danson S et al. Cancer 2003; 98: 542 553 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Gemcitabine /carboplatin



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GEMCITABINE (NSCLC) NICE guidance – www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine should each be considered as part of firstline chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: Palliative treatment of NSCLC when patient not fit enough to tolerate platinum (e.g. performance status 2) DRUG REGIMEN Day 1 GEMCITABINE 1g/m2


Day 8 GEMCITABINE 1g/m2

infusion in 250ml sodium chloride 0.9% over 30 minutes Day 15 GEMCITABINE 1g/m2


Cycle Frequency: Every 28 days Number of cycles: Up to 4 (subject to tolerance and response) DOSE MODIFICATIONS CrCl <30ml/min consider dose reduction (Clinical decision) If bilirubin >27micromol/L initiate treatment with dose of 800mg/m2 Neutrophils >1.5x10x9/L and platelets >100x10x9/L give 100% dose (Day 1 and 8) Neutrophils 0.5-1.5x10x9/L or platelets 50-100x10x9/L give 75% dose (Day 8 only) or delay based on clinical assessment (Day 1 and 8) Neutrophils <0.5x10x9/L or platelets <50x10x9/L delay treatment (Day 1) or omit treatment (Day 8). Diarrhoea and/or mucositis Grade 2 toxicity – omit until toxicity resolved then restart at 100% dose Grade 3 toxicity – omit until toxicity resolved then restart at 75% dose Grade 4 toxicity – omit until toxicity resolved then restart at 50% dose INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests. Tests relating to disease response/progression Gemcitabine Lung TSSG Chair Authorisation:

Date:


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CONCURRENT MEDICATION ANTIEMETIC POLICY Low emetic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Diarrhoea – see dose modifications treat with loperamide or codeine. Mucositis – see dose modifications use routine mouth care. REFERENCES 1. Gridelli C et al. Journal of the National Cancer Institute 2003; 95: 363 372 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Gemcitabine Lung TSSG Chair Authorisation: Date:


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PACLITAXEL 80mg (7 day) Indication: NSCLC DRUG REGIMEN Day 1 PREMEDICATION 30mins prior to infusion:

DEXAMETHASONE 8mg IV bolus RANITIDINE 50mg IV bolus CHLORPHENAMINE 10mg IV bolus PACLITAXEL 80mg/m2

in 250ml sodium chloride 0.9% infusion over 1 hour

Cycle Frequency: Days 1, 8 and 15 every 28 days up to 3 cycles subject to tolerance and response DOSE MODIFICATIONS If patient complains of tinnitus, tingling of fingers and/or toes or motor weakness discuss with Consultant or Registrar before administration. In the absence of Gilbert's syndrome: Bilirubin >51micromol/L stop treatment INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Liver function tests (LFT) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Ensure pre-medication is given.

Paclitaxel 80mg weekly q28d



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ANTIEMETIC POLICY Low emetogenic risk ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS (2% risk of severe hypersensitivity) Reactions range from mild hypotension (light-headedness) to full cardiac collapse (anaphylactic shock). Discontinue infusion and resuscitate appropriate to reaction. If reaction is mild and settles promptly (i.e. within 5-10 minutes), cautiously restart at a slower rate under close supervision. If further reactions occur stop treatment.

Paclitaxel 80mg weekly q28d



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VINORELBINE (25) CARBOPLATIN (NSCLC) NICE guidance www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: Palliative treatment of NSCLC. DRUG REGIMEN Day 1 VINORELBINE 25mg/m2

in 50ml sodium chloride 0.9% IV infusion over 10 mins

CARBOPLATIN (AUC = 5*) in 500ml glucose 5% over 1 hour Dose = (25 + GFR) x AUC

Day 8 VINORELBINE 25mg/m2 in 50ml sodium chloride 0.9% IV infusion over 10 mins

Cycle Frequency: Every 21 days Number of cycles: 2 or 3 if given in neoadjuvant and adjuvant setting, up to 4 in palliative setting (subject to tolerance and response) NB *Ideally EDTA GFR should be used, If GFR is measured or EDTA then: AUC = 5 If calculated from serum creatinine the result is less accurate DOSE MODIFICATIONS Previous neutropenic sepsis, discuss with Consultant or Registrar Vinorelbine: If there is significant hepatic impairment the dose should be reduced If bilirubin > 2 x ULN and AST/ALT >5 x ULN give 66.6% dose Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If GFR/ calculated CrCl = or < 20ml/min contraindicated Vinorelbine/ carboplatin



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GFR should be measured using EDTA clearance. Estimating creatinine clearance from the serum creatinine, weight and age is less accurate. Liver function tests (LFTs) 2) Non urgent blood tests Tests relating to disease response/progression CONCURRENT MEDICATION Anaphylaxis treatment should be prescribed if the patient has had an anaphylactic episode previously. DEXAMETHASONE 20mg IV bolus CHLORPHENAMINE 10mg IV bolus RANITIDINE 50mg IV bolus Carboplatin should be given at a slower rate e.g. 2-4 hours. ANTIEMETIC POLICY Moderate emetic risk day 1 Minimal emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Ototoxicity - monitor Neurotoxicity – monitor

REFERENCES 1. Baldini E et al. Br J Cancer 1998; 77: 2367 2370. 2. Cremonesi M et al. Oncology 2003; 64 : 97-101 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Vinorelbine/ carboplatin



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VINORELBINE (25) CISPLATIN (80) (NSCLC) NICE guidance www.nice.org.uk. Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. 4 cycles of vinorelbine plus cisplatin are indicated for adjuvant treatment of patients following complete resection of non small cell lung cancer Indication: Palliative treatment of unresectable NCSLC. Also used as neoadjuvant treatment prior to radical chemoradiotherapy and adjuvant treatment of patients following complete resection of non small cell lung cancer DRUG REGIMEN Day 1 Pre-hydration

VINORELBINE 25mg/m2

in 50ml sodium chloride 0.9% IV infusion over 10 mins CISPLATIN 80mg/m2


Post-hydration Day 8 VINORELBINE 25mg/m2


Cycle Frequency: Every 21 days Number of cycles: 2 or 3 if given in neoadjuvant and adjuvant setting, up to 4 in palliative setting (subject to tolerance and response) DOSE MODIFICATIONS Vinorelbine: If there is significant hepatic impairment the dose should be reduced If bilirubin > 2 x ULN and AST/ALT >5 x ULN give 66.6% dose Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration.

Vinorelbine / cisplatin



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Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion (Cisplatin). Liver function tests (LFTs) 2) Non urgent blood tests. Tests relating to disease response/progression CONCURRENT MEDICATION Ensure adequate pre and post hydration prescribed as per day case schedule at the end of TVCN protocols. If urine output is <100 ml/hour or if patient gains >2kg in weight during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. . ANTIEMETIC POLICY High emetic risk day 1 Minimal emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Wozniak AJ et al. J Clin Oncol 1998; 16: 2459 2465 2. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Vinorelbine / cisplatin



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VINORELBINE (NSCLC) NICE guidance – www.nice.org.uk Docetaxel, gemcitabine, paclitaxel and vinorelbine should each be considered as part of first-line chemotherapy options for advanced (stage III and IV) NSCLC patients. Indication: Palliative treatment of NSCLC when patient not fit enough to tolerate platinum (e.g. performance status 2)

DRUG REGIMEN Day 1 VINORELBINE 30 mg/m2


Day 8 VINORELBINE 30 mg/m2

in 50ml sodium chloride 0.9% IV infusion over 10 mins Administration should always be followed by a 250ml sodium chloride 0.9% infusion to flush the vein. Cycle Frequency: Every 21 days Number of cycles: Individualised but rarely more than 4

DOSE MODIFICATIONS If there is significant hepatic impairment the dose should be reduced If bilirubin > 2 x ULN and AST/ALT >5 x ULN give 66.6% dose


Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests - Tests relating to disease response/progression

CONCURRENT MEDICATION

ANTIEMETIC POLICY Minimal emetic risk.

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS REFERENCES 1. Gridelli C et al. Oncologist 2001; 6: Supp 1: 4 7 Vinorelbine Lung TSSG Chair Authorisation:

Date:


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VINORELBINE (oral) (NSCLC) NICE guidance www.nice.org.uk. Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. 4 cycles of vinorelbine plus cisplatin are indicated for adjuvant treatment of patients following complete resection of non small cell lung cancer Indication: Palliative treatment of stage III or IV NSCLC or patients not fit enough to tolerate platinum DRUG REGIMEN Cycle 1 Day 1, 8 and 15 VINORELBINE 60mg/m2

orally once a week. (Maximum dose 160 mg/week) Cycle 2 onwards - dose escalation at the Consultant’s discretion if cycle 1 tolerated Day 1, 8 and 15 VINORELBINE 80mg/m2

orally once a week (see dose modifications) (Maximum dose 160 mg/week)

NB capsules should be swallowed with food and water without chewing or sucking the capsule at least 30 minutes after antiemetic. Available as 20, 30, 40 and 80mg capsules NB Based on clinical studies, the oral dose of 80 mg/m2 was demonstrated to correspond to 30 mg/m2 of the iv form and 60 mg/m2 to 25 mg/m2

Cycle Frequency: every 21 days DOSE MODIFICATIONS AND DELAYS Dose escalation from cycle 2 onwards to 80mg/m2

except in patients for whom the neutrophil count

has dropped once below 0.5 x109/L OR more than once between 0.5-1.0 x109/L during the first cycle doses, in these patients continue at 60mg/m2

For doses planned to be given at 80mg/m², if the neutrophil count is below 0.5 x109/L OR more than once between 0.5-1.0 x109/L administration should be delayed until recovery and the dose reduced from 80 to 60mg/m2 per week during the following cycles. If the neutrophil count is below 1.5 x109/L AND/OR the platelet count is between 75-100 x109/L then the treatment should be delayed until recovery

Vinorelbine PO



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Hepatic impairment No prospective study is available in order to establish guidelines for the dose reduction of vinorelbine capsules. If there is significant hepatic impairment the dose of Vinorelbine soft capsules should be reduced. In patients with massive liver metastases (i.e.> 75% of liver volume replaced by the tumour) it is empirically suggested that a 75% dose be given and the haematological parameters closely monitored. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Liver function tests (LFTs) 2) Non urgent blood tests.- Tests relating to disease response/progression CONCURRENT MEDICATION Cytochrome P450 is likely to be mainly involved in the metabolism of vinorelbine, combination with inducers or inhibitors of this isoenzyme may alter its pharmacokinetics. Omeprazole and fluoxetine (norfluoxetine), inhibitors for CYP3A4, were both found to moderately inhibit the metabolism of vinorelbine, although the clinical relevance of this inhibition is not known ANTIEMETIC POLICY Moderate emetic risk days 1 and 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Vinorelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver. REFERENCES 1. NAVELBINE soft capsules http://emc.medicines.org.uk [accessed 25/03/08]

Vinorelbine PO



Version 3.4

Thames Valley


VINORELBINE elderly (oral) (NSCLC) NICE guidance www.nice.org.uk. Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. 4 cycles of vinorelbine plus cisplatin are indicated for adjuvant treatment of patients following complete resection of non small cell lung cancer Indication: Palliative treatment of stage III or IV NSCLC or patients not fit enough to tolerate platinum DRUG REGIMEN Cycle 1 Day 1 and 8 VINORELBINE 60mg/m2

orally. (Maximum dose 160 mg/week) Cycle 2 onwards - dose escalation at the Consultant’s discretion if cycle 1 tolerated Day 1 and 8 VINORELBINE 80mg/m2

(see dose modifications, (Maximum dose 160 mg/week)

NB capsules should be swallowed with food and water without chewing or sucking the capsule at least 30 minutes after antiemetic. Available as 20, 30, 40 and 80mg capsules NB Based on clinical studies, the oral dose of 80 mg/m2 was demonstrated to correspond to 30 mg/m2 of the iv form and 60 mg/m2 to 25 mg/m2

Cycle Frequency: every 21 days DOSE MODIFICATIONS AND DELAYS Dose escalation from cycle 2 onwards to 80mg/m2



For doses planned to be given at 80mg/m², if the neutrophil count is below 0.5 x109/L OR more than once between 0.5-1.0 x109/L administration should be delayed until recovery and the dose reduced from 80 to 60mg/m2 per week during the following cycles. If the neutrophil count is below 1.5 x109/L AND/OR the platelet count is between 75-100 x109/L then the treatment should be delayed until recovery

Vinorelbine elderly PO



Version 3.4

Thames Valley


Hepatic impairment No prospective study is available in order to establish guidelines for the dose reduction of Vinorelbine capsules. If there is significant hepatic impairment the dose of Vinorelbine soft capsules should be reduced. In patients with massive liver metastases (i.e.> 75% of liver volume replaced by the tumour) it is empirically suggested that a 75% dose be given and the haematological parameters closely monitored. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Liver function tests (LFTs) 2) Non urgent blood tests.- Tests relating to disease response/progression CONCURRENT MEDICATION Cytochrome P450 is likely to be mainly involved in the metabolism of vinorelbine, combination with inducers or inhibitors of this isoenzyme may alter its pharmacokinetics. Omeprazole and fluoxetine (norfluoxetine), inhibitors for CYP3A4, were both found to moderately inhibit the metabolism of vinorelbine, although the clinical relevance of this inhibition is not known ANTIEMETIC POLICY Moderate emetic risk days 1 and 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Vinorelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver. REFERENCES 1. NAVELBINE soft capsules http://emc.medicines.org.uk [accessed 25/03/08]

Vinorelbine elderly PO



Version 3.4

Thames Valley


VINORELBINE (oral) CISPLATIN (NSCLC) NICE guidance www.nice.org.uk. Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. 4 cycles of vinorelbine plus cisplatin are indicated for adjuvant treatment of patients following complete resection of non small cell lung cancer Indication: Palliative treatment of unresectable NCSLC. Adjuvant treatment following complete resection of NSCLC. Also used as neoadjuvant treatment prior to radical chemoradiotherapy DRUG REGIMEN Cycle 1 Day 1 Pre-hydration

VINORELBINE 60mg/m2

orally (Maximum dose 160mg/week) CISPLATIN 80mg/m2


Post-hydration Day 8 VINORELBINE 60mg/m2

orally (Maximum dose 160mg/week) Cycle 2 onwards - dose escalation at the Consultant’s discretion if cycle 1 tolerated Day 1 Pre-hydration

VINORELBINE 80mg/m2

orally (Maximum dose 160mg/week) CISPLATIN 80mg/m2


(daypatient) or 4 hours (inpatient) Post-hydration Day 8 VINORELBINE 80mg/m2

orally (Maximum dose 160mg/week) NB capsules should be swallowed with food and water without chewing or sucking the capsule at least 30 minutes after antiemetic. Available as 20, 30, 40 and 80mg capsules NB Based on clinical studies, the oral dose of 60mg/m2 was demonstrated to correspond to 25mg/m2 of the iv form and 80mg/m2 to 30mg/m2, Vinorelbine dose may be increased to 80mg/m2 Cycle Frequency: Every 21 days Number of cycles: 2 or 3 if given in neoadjuvant setting, up to 4 in palliative setting, 4 cycles for adjuvant treatment following complete resection (subject to tolerance and response)

Vinorelbine PO/ cisplatin



Version 3.4

Thames Valley


DOSE MODIFICATIONS AND DELAYS Dose escalation from cycle 2 onwards to 80mg/m2



For doses planned to be given at 80mg/m², if the neutrophil count is below 0.5 x109/L OR more than once between 0.5-1.0 x109/L administration should be delayed until recovery and the dose reduced from 80 to 60mg/m2 per week during the following cycles. I If the neutrophil count is below 1.5 x109/L AND/OR the platelet count is between 75-100 x109/L then the treatment should be delayed until recovery Hepatic impairment No prospective study is available in order to establish guidelines for the dose reduction of Vinorelbine capsules. If there is significant hepatic impairment the dose of Vinorelbine soft capsules should be reduced. In patients with massive liver metastases (i.e.> 75% of liver volume replaced by the tumour) it is empirically suggested that the dose be reduced by 25 % and the haematological parameters closely monitored. Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR < 40ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration. INVESTIGATIONS Routine Blood test 1) Blood results required before chemotherapy administration

Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion (Cisplatin). Liver function tests (LFTs) 2) Non urgent blood tests- Tests relating to disease response/progression




Version 3.4

Thames Valley


CONCURRENT MEDICATION Cisplatin - Ensure adequate pre-and post-hydration prescribed as per inpatient schedule at the end of the TVCN protocols. If fluid balance is > 2L positive after 8 hours post hydration OR if patient gains >2kg in weight or urine output <100ml/hour during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. Vinorelbine- Cytochrome P450 is likely to be mainly involved in the metabolism of vinorelbine, combination with inducers or inhibitors of this isoenzyme may alter its pharmacokinetics. Omeprazole and fluoxetine (norfluoxetine), inhibitors for CYP3A4, were both found to moderately inhibit the metabolism of vinorelbine, although the clinical relevance of this inhibition is not known ANTIEMETIC POLICY High emetic risk day 1 Moderate emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Vinorelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver. REFERENCES 1. Wozniak AJ et al. J Clin Oncol 1998; 16: 2459 2465 2. NAVELBINE soft capsules http://emc.medicines.org.uk [accessed 25/03/08] 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic





Version 3.4

Thames Valley


VINORELBINE (oral) CARBOPLATIN (NSCLC) NICE guidance www.nice.org.uk. Docetaxel, gemcitabine, paclitaxel and vinorelbine, with a platinum drug, should each be considered as part of first line chemotherapy options for advanced (stage III and IV) NSCLC patients. 4 cycles of vinorelbine plus cisplatin are indicated for adjuvant treatment of patients following complete resection of non small cell lung cancer Indication: Palliative treatment of unresectable NCSLC. Also used as neoadjuvant treatment prior to radical chemoradiotherapy DRUG REGIMEN Day 1 VINORELBINE 60mg/m2

orally (maximum dose 160mg/week) CARBOPLATIN AUC5 in 500ml glucose 5% infusion over 60 minutes

Day 8 VINORELBINE 60mg/m2 orally (maximum dose 160mg/week)

NB capsules should be swallowed with food and water without chewing or sucking the capsule at least 30 minutes after antiemetic. Available as 20, 30, 40 and 80mg capsules NB Based on clinical studies, the oral dose of 60mg/m2 was demonstrated to correspond to 25mg/m2 of the iv form and 80mg/m2 to 30mg/m2, Vinorelbine dose may be increased to 80mg/m2 Cycle Frequency: Every 21 days Number of cycles: 2 or 3 if given in neoadjuvant setting, up to 4 in palliative setting (subject to tolerance and response) DOSE MODIFICATIONS AND DELAYS Hepatic impairment No prospective study is available in order to establish guidelines for the dose reduction of Vinorelbine capsules. If there is significant hepatic impairment the dose of Vinorelbine soft capsules should be reduced. In patients with massive liver metastases (i.e.> 75% of liver volume replaced by the tumour) it is empirically suggested that the dose be reduced by 25 % and the haematological parameters closely monitored. Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If EDTA GFR = or < 20ml/min contraindicated Vinorelbine PO/ carboplatin



Version 3.4

Thames Valley



Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Creatinine clearance (GFR) calculated OR EDTA at the Consultants discretion (Carboplatin). Liver function tests (LFTs) 2) Non urgent blood tests- Tests relating to disease response/progression CONCURRENT MEDICATION Vinorelbine- Cytochrome P450 is likely to be mainly involved in the metabolism of vinorelbine, combination with inducers or inhibitors of this isoenzyme may alter its pharmacokinetics. Omeprazole and fluoxetine (norfluoxetine), inhibitors for CYP3A4, were both found to moderately inhibit the metabolism of vinorelbine, although the clinical relevance of this inhibition is not known ANTIEMETIC POLICY High emetic risk day 1 Moderate emetic risk day 8 ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. Vinorelbine should not be given concomitantly with radiotherapy if the treatment field includes the liver. REFERENCES 1. Wozniak AJ et al. J Clin Oncol 1998; 16: 2459 2465 2. NAVELBINE soft capsules http://emc.medicines.org.uk [accessed 25/03/08] 3. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic

impairment. 2009, The North London Cancer Network

Vinorelbine PO/ carboplatin



Version 3.4

Thames Valley


CARBOPLATIN PEMETREXED (Mesothelioma / NSCLC)

NICE: Pemetrexed is recommended as a possible treatment for malignant pleural mesothelioma in people: with advanced disease whose cancer is not suitable for surgical resection (removal) and who have a WHO performance status of 0 or 1 Pemetrexed is recommended as 1st line treatment of NSCLC adenocarcinoma and large cell undifferentiated carcinoma. Indication: Palliative treatment of non-resectable malignant mesothelioma in patient with an ECOG performance status of 0-1. First line treatment of Non-small cell lung cancer.

DRUG REGIMEN Day 1 Pre-medication

Dexamethasone 4mg bd for 3 days (starting the day before chemotherapy) Folic acid 400mcg/day orally starting 1 to 3 weeks before chemotherapy continuing until 21 days after the last dose of pemetrexed. Hydroxycobalamin 1000mcg IM every 9 weeks starting 1 to 3 weeks before chemotherapy (give with every 3rd cycle of chemotherapy) PEMETREXED 500mg/m2 IV infusion in 100ml sodium chloride 0.9% over 10 mins CARBOPLATIN AUC 5 IV infusion in 500ml glucose 5% over 60 minutes

(30 minutes after completing Pemetrexed)

Cycle frequency: Every 21 days Number of cycles: Plan for 3 cycles and repeat cross sectional imaging and full

assessment. Maximum 6 cycles depending on tolerance and response.

DOSE MODIFICATIONS Pemetrexed: Delay treatment until resolution then treat with appropriate dose modification. Nadir neutrophils <0.5 and nadir platelets >50 75% of previous dose Nadir platelets 50 regardless of nadir neutrophils 50% of previous dose Any Grade 3 or 4 non-haematological toxicities except mucositis 75% of previous dose Any diarrhoea requiring hospitalisation (irrespective of grade) 75% of previous dose or Grade 3 or 4 diarrhoea Grade 3 or 4 mucositis 50% of previous dose Neurotoxicity grade 3 or 4 Discontinue therapy

Carboplatin / Pemetrexed



Version 3.4

Thames Valley


Treatment with pemetrexed should be discontinued if a patient experiences any haematologic or non-haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed. Creatinine clearance (GFR) should be 45ml/min (calculated or EDTA) otherwise clinical decision Liver function tests (LFTs) Total bilirubin should be 1.5 x upper limit of normal. Alk phos, AST and ALT 3 x upper limit of normal. (Alk phos, AST, and ALT 5 x normal is acceptable if liver has tumour involvement). Clinical decision Carboplatin: Discuss if patient has a serum creatinine > 150 micromol/L If GFR/ calculated CrCl = or < 20ml/min contraindicated


Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests Tests relating to disease response/progression Ideally EDTA GFR should be used (Carboplatin) Creatinine clearance (GFR) calculated, at the Consultants discretion Liver function tests (LFT)

CONCURRENT MEDICATION Avoid use of high dose NSAIDs with CrCl > 80ml/min. Avoid all NSAIDS with CrCl between 45 and 79ml/min for at least 5 days prior to and 2 days after pemetrexed dose.

ANTI-EMETIC POLICY High emetic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities. REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Carboplatin / Pemetrexed



Version 3.4

Thames Valley


CISPLATIN PEMETREXED (Mesothelioma / NSCLC)

NICE: Pemetrexed is recommended as a possible treatment for malignant pleural mesothelioma in people: with advanced disease whose cancer is not suitable for surgical resection (removal) and who have a WHO performance status of 0 or 1 Pemetrexed is recommended as 1st line treatment of NSCLC adenocarcinoma and large cell undifferentiated carcinoma.

Indication: Palliative treatment of non-resectable malignant mesothelioma in patient with an ECOG performance status of 0-1. First line treatment of Non-small cell lung cancer.


Dexamethasone 4mg bd for 3 days (starting the day before chemotherapy) Folic acid 400mcg/day orally starting 1 to 3 weeks before chemotherapy continuing until 21 days after the last dose of pemetrexed. Hydroxycobalamin 1000mcg IM every 9 weeks starting 1 to 3 weeks before chemotherapy (give with every 3rd cycle of chemotherapy)

Pre-hydration PEMETREXED 500mg/m2 IV infusion in 100ml sodium chloride 0.9% over 10 mins CISPLATIN 75mg/m2 IV infusion in 1000ml sodium chloride 0.9% over 2 hours (30 minutes

after completing Pemetrexed) Post-hydration

Cycle frequency: Every 21 days Number of cycles: Plan for 3 cycles and repeat cross sectional imaging and full

assessment. Maximum 6 cycles depending on tolerance and response.


Treatment with pemetrexed should be discontinued if a patient experiences any haematologic or non-haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.

Cisplatin / Pemetrexed



Version 3.4

Thames Valley


Creatinine clearance (GFR) should be 45ml/min (calculated or EDTA). Clinical decision Liver function tests (LFTs) Total bilirubin should be 1.5 x upper limit of normal. Alk phos, AST and ALT 3 x upper limit of normal. (Alk phos, AST, and ALT 5 x normal is acceptable if liver has tumour involvement). Clinicial decision Cisplatin: GFR >60ml/min give 100% dose GFR 45-60ml/min give 75% dose GFR <45ml/min consider carboplatin If patient complains of tinnitus, tingling of fingers and/or toes, discuss with SpR or Consultant before administration.


Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests Tests relating to disease response/progression

CONCURRENT MEDICATION Ensure adequate pre-and post-hydration prescribed as per inpatient schedule at the end of the TVCN protocols. If fluid balance is > 2L positive after 8 hours post hydration OR if patient gains >2kg in weight or urine output <100ml/hour during IV administration post Cisplatin give 20 - 40 mg Furosemide PO/IV OR 200ml Mannitol 10% IV. Dexamethasone 4mg bd for 3 days (starting the day before chemotherapy) Avoid use of high dose NSAIDs with CrCl > 80ml/min. Avoid all NSAIDS with CrCl between 45 and 79ml/min for at least 5 days prior to and 2 days after pemetrexed dose.

ANTI-EMETIC POLICY High emetic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS Nephrotoxicity – ensure adequate pre and post hydration is prescribed. Ototoxicity – assess patient for tinnitus or hearing abnormalities.

REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Cisplatin / Pemetrexed



Version 3.4

Thames Valley


PEMETREXED maintenance (NSCLC)

Indication: Locally advanced or metastatic non-small cell lung cancer following treatment with permetrexed and cisplatin. Ensure funding is available prior to prescribing


Dexamethasone 4mg bd for 3 days (starting the day before chemotherapy) Folic acid 400mcg/day orally starting 1 to 3 weeks before chemotherapy continuing until 21 days after the last dose of pemetrexed. Hydroxycobalamin 1000mcg IM every 9 weeks starting 1 to 3 weeks before chemotherapy (give with every 3rd cycle of chemotherapy)

PEMETREXED 500mg/m2 IV infusion in 100ml sodium chloride 0.9% over 10 mins

Cycle frequency: Every 21 days Number of cycles: Maintenance


Treatment with pemetrexed should be discontinued if a patient experiences any haematologic or non-haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed. Creatinine clearance (GFR) should be 45ml/min (calculated or EDTA). Clinical decision Liver function tests (LFTs) Total bilirubin should be 1.5 x upper limit of normal. Alk phos, AST and ALT 3 x upper limit of normal. (Alk phos, AST, and ALT 5 x normal is acceptable if liver has tumour involvement). Clinicial decision

Pemetrexed maintenance



Version 3.4

Thames Valley



Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 2) Non urgent blood tests Tests relating to disease response/progression

CONCURRENT MEDICATION Dexamethasone 4mg bd for 3 days (starting the day before chemotherapy) Avoid use of high dose NSAIDs with CrCl > 80ml/min. Avoid all NSAIDS with CrCl between 45 and 79ml/min for at least 5 days prior to and 2 days after pemetrexed dose.

ANTI-EMETIC POLICY Low emetic risk

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS

REFERENCES 1. Daniels, S. and S. Gabriel, Dosage adjustment for cytotoxics in renal impairment and hepatic


Pemetrexed maintenance



Version 3.4

Thames Valley


Pre-hydration and post-hydration regimens Ensure adequate diuresis is obtained prior to administration and maintained during and after administration. 1. Inpatient

Pre 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours Give cisplatin in 1000ml volume over 4 hours Post 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 4 hours

NB 1L sodium chloride 0.9% + 20mmol KCl + 8mmol MgSO4 infusion over 6 hours if oral intake is inadequate

2. Day case Pre 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours 200ml mannitol 10% infusion over 30 minutes (immediately before cisplatin) Give cisplatin in 1000ml volume over 2 hours Post 1L sodium chloride 0.9% + 20 mmol KCl + 8mmol MgSO4 infusion over 2 hours

NB Furosemide 40mg may be added if required

Hydration Lung TSSG Chair Authorisation: Date


Version 2.4

Thames Valley


Common Toxicity Criteria Toxicity 0 1 2 3 4 Allergic None Transient rash,

drug fever <38C (100.4F)

Urticaria, drug fever 38C (100.4F) and/or asymptomatic bronchospasm

Symptomatic bronchospasm requiring parenteral medication(s) with or without urticaria; allergy related oedema / angioedema

Anaphylaxis

Alopecia Normal Mild hair loss Pronounced hair loss

- -

Anorexia None Loss of appetite Oral intake significantly decreased

Requiring IV fluids Requiring feeding tube or parenteral nutrition

Blood counts Neutrophils

Within normal limits

1.5x109/l - normal 1.0-1.4x109/l 0.5-0.9x109/l <0.5x109/l

Blood counts Haemoglobin


10.0g/dl – normal 8.0 9.9g/dl 6.5-7.9g/dl <6.5g/dl

Blood counts Platelets


75x109/l - normal 50-74x109/l 10-49x109/l <10x109/l

Blood counts White blood count


3.0x109/l - normal 2.0-2.9x109/l 1.0-1.9x109/l <1.0x109/l

Diarrhoea (patients with colostomy)

None Mild increase in loose, watery colostomy output compared with pre-treatment

Moderate increase in loose, watery colostomy output compared with pre-treatment, but not interfering with normal activity

Severe increase in loose, watery colostomy output compared with pre-treatment, interfering with normal activity

Physiologic consequences requiring intensive care, or haemodynamic collapse

Diarrhoea (patients without colostomy)

None Increase of <4 stools/day over pre-treatment

Increase of 4-6 stools/day, or nocturnal stools

Increase of 7 stools/day, or incontinence; or need for parenteral support for dehydration

Physiological consequences requiring intensive care, or haemodynamic collapse

Hand-foot skin reaction

None Skin changes or dermatitis without pain

Skin changes with pain, not interfering with function

Skin changes with pain, interfering with function

-

Hepatic – alk phos

ULN >ULN – 2.5x ULN >2.5 – 5.0xULN 5.0 – 20.0xULN >20.0XULN

Hepatic – bilirubin

ULN >ULN – 1.5x ULN >1.5 – 3.0xULN 3.0 – 10.0xULN >10.0XULN

Thames Valley


Lethargy None Increased fatigue over baseline, but not altering normal activities

Moderate (decrease in performance status by level 1) or causing difficulty performing some activities

Severe (decrease in performance status by 2 levels), or loss of ability to perform some activities

Bedridden or disabling

Nausea None Able to eat Oral intake significantly decreased

No significant intake, requiring IV fluids

-

Neuropathy - motor

Normal Subjective weakness but no objective findings

Mild objective weakness interfering with function, but not interfering with activities of daily living

Objective weakness interfering with activities of daily living

Paralysis

Neuropathy - sensory

Normal Loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function

Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living

Sensory loss of paresthesia interfering with activities of daily living

Permanent sensory loss that interferes with function

Pain None Mild pain not interfering with function

Moderate pain: pain or analgesics interfering with function but not interfering with activities of daily living

Severe pain: pain or analgesics severely interfering with activities of daily living

Disabling

Stomatitis None Painless ulcers, erythema or mild soreness

Painful erythema, oedema or ulcers but can eat or swallow

Painful erythema oedema, or ulcers requiring IV hydration

Severe ulceration or requires parenteral or enteral nutritional support or prophylactic intubation

Vomiting None 1 episode in 24 hours

2-5 episodes in 24 hours

6 episodes in 24 hours, or need for IV fluids

Requiring parenteral nutrition, or physiological consequences requiring intensive care; haemodynamic collapse

thames valley chemotherapy regimens - tvscn

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